J. Org. C h e m . 1992,57,6496+3502
6496
Reaction of p-Oxobis[(trifluoromethanesulfonato)(phenyl)iodine(III)] with Group 14 Propargyl Derivatives and a Propargyl Ether Daniel A. Gately, Thomas A. Luther, Jack R. Norton,* Mary M. Miller, and Oren P. Anderson Department of Chemistry, Colorado State University, Fort Collins, Colorado 80623 Received June 1, 1992
The treatment of 4,4dimethyl-l-(trimethylsilyl)-2-pntyne (4a)or 4,4dimethyl-l-(tributylstannyl)-2-pntyne (ab)with p-oxobie[ (trifluoromethanesulfoaato)henyl)iodine(m)] (2) gim 4,4dimethyl-l-(%iodophenyl)-2-pentyne (9). Deuterium labeling has confiied that propargylation of 2 occurs ortho to the position originally occupied by the I(II1). The addition of 2 equiv of 4a to 2 at -80 "C results in 2 equiv each of 9, trimethylsilyl triflate
(lo), and tert-butylallene (11) and 1 equiv of hexamethyldisiloxane(12);in contrast, the addition of 2 equiv of
4b to 2 at -30 "C results in 2 equiv each of 9 and tributylstannyl triflate (16). A mechanism that explains these product ratios ie proposed. The reaction of 2-0,0'-d2and 4b shows the negligible intramolecular kinetic isotope effect (0.99 f 0.01) expected for what is in effect a Claisen rearrangement. The addition of 2 to 2-butynyl (trimethylsily1)methyl ether (20) affords the single product 21 resulting from anti addition and control of regiochemistry by the ether oxygen. Attempts to desilylate 21 to an allenyl triflate result in the regeneration of the propargyl ether 20.
Introduction Wenes are directly and indirectly involved in substitution and elimination processc-, sigmatropic rearrangemente, and cycloaddition reactions with allenes, ketenes, olefins, enones, and heterocycles.' An allenyl triflate or iodinane would be synthetically equivalent to an sp2carbocation 1 in the m e way that vinyl triflates2 and iodinanes3are equivalent to sp2carbocations and alkynyl esters: iodinanes,6 and diiodinanesa are equivalent to sp carbocations. R
XA+--
L
Scheme I
3
P
1%
B
-
-
=
(allenyl uiflate)
R\==
+
1
Our fmt effort to generate an allenyl triflate or iodinane began with the reaction of alkynes with the diary1 di(1) For a comprehensive review of allenes, see: (a) The Chemistry of Allenes; Landor, S . R., Ed.; Academic: London, 1982; Vole. 1-3. (b) Schwter, H. F.; Coppola, G. M. Allenes in Organic Synthesis; Wiley: New York, 1984. (2) For reviews of vinyl triflates, see: (a) Stang, P. J.; Hanack, M.; Subramanian, L. R. Synthesis 1982,s. (b) Stang, P. J.; Rappaport, Z.; Hanack, M.;Subramanian, L. R. Vinyl Cations; Academic Press, New York, 1979. (c) Stang, P. J. Acc. Chem. Res. 1978, 11, 107. (d) Subramanian, L. R.; Hanack, M. J. Chem. Educ. 1975,52,80. (e) Stang, P. J. R o g . Phys. Org. Chem. 1973,10,205. (0Modena, G.;Tonelato, U. Adv. Phys. Chem. 1971,9,185. (3) F?r the synthesis and reactivity of vinyl iodinanes, see: (a) Ochiai, M.; Oduma, K.; Masaki, Y. J. Am. Chem. SOC.1991,113,7059. (b) Stang, P. J.; ullmann,J. Angew. Chem.,Znt.Ed. Engl. 1991,11,1469. (c) Ochiai, M.; Oshima, K.; Maaaki, Y. J. Chem. SOC.,Chem. Commun. 1991,869. (d) Ochiai, M.; S u i , K.; Takaoka, Y.; Kunishima, M.; Nagao, Y.; Shiro, M.; Fujita, E. Tetrahedron Lett. 1988,44,4095. (e) Ochiai, M.; Sumi, K.; Nagao, Y.; Fujita, V. Tetrahedron Lett. 1985,26,2351. (0Neameyanov, A. N.; Tolataya, T. P.; Petrakov, A. V.; Goletev, A. N. Dokl. Akad. Nauk. SSSR 1977,235, 591. (g) Nesmeyanov, A. N.; Toletaya, T. P.; Petrakov, A. V. Dokl. Akad. Nauk. SSSR 1971,197, 1337. (4) For a recent review of alkynyl esters, see: (a) Stang, P. J. Angew. Chem., Int. Ed. Engl. 1992,3,274. (b) Stang, P. J. Acc. Chem. Res. 1991, 24,304. (5) For the synthesia and reactivity of alkynyl iodinanes, see: (a) Stang,P. J.; Arif,A. M.; Critell, C. M.Angew. Chem., Int. Ed. Engl. 1990, 3,287. (b) Kitamura, T.; Stang, P. J. J. Org. Chem. 1988,53,4105. (c)
Stang, P. J.; Surber, B. W.; Chen, Z. C.; Roberta, K. A,; Anderson, A.
G.
J. Am. Chem. SOC. 1987,109,228. (d) Ochiai, M.; Kunishima, M.; Sumi, K.; Nagao, Y.; Fujita, E.;Arimoto, M.; Yamaguchi, H. Tetrahedron Lett. 1985,26,4501. (e) Rabrovic,L.; Kceer, G.F. J. Org. Chem. 1984,49,4700. (0Koeer, G.F.; Rebrovic,L.; Wettach, R. H. J. Org. Chem. 1981,46,4324. (g) Also see ref 4a and b. (6) For the synthesis and reactivity of alkynyl diiodanes, see: (a) Stang,P. J.; Zhdankin, V. V. J. Am. Chem. SOC.1991, 113, 4571. (b) Stang, P. J.; Zhdankin, V. V. J. Am. Chem. SOC.1990, 112, 6437.
iodinane p-oxobis[ (trifluoromethanesulfonato)(phenyl)iodine(III)](2) (Zefirov's reagent)? The reaction of simple olefins with 2 is known to afford vicinal ditriflates by syn additionFs presumably by the process in eq 1. With alkynes one would expect the process to stop after anti addition and formation of a vinyliodonium triflate as in eq 2.
m-
-m
TIC
When we began this work little was known about the reactivity of symmetrical or unsymmetricalsalkynes with iodine(II1) reagents.1° We obtained a single product 3 (7) (a) Zefirov, N. S.;Zhdankin, V. V.; Dan'kov, Y. V.; Koz'min, A. S. J. Org. Chem. USSR (Engl. Trans.) 1984,20,401; Zh. Org. Khim. 1984, 20,446. (b) Galloa, J.; Varvcglis, A.; Alcock, N. W. J. Chem. SOC.,Perkin 7'rans. I 1985,757. (c) Hembre, R. T.; Scott, C. P.; Norton, J. R. J. Org. Chem. 1987,52,3650. (8) (a) Zefirov, N. S.; Zhdnukin, V. V.; Dan'kov, Y.V.; Sovokin, V. D.; Semerikov, V. N.; Koz'min, A. S.; Caple, R.; Berglund, B. A. Tetrahedron Lett. 1986,27,3971. (b) Zefirov, N. S.; Koz'min, A. S.Acc. Chem. Res. 1985,18, 154. (9) Stang and co-workers recently established the regioeelective anti addition of PhIOH(0TfJ 17 to terminal acetylenes, see: Kitamura, T.; Taniguchi, H.;Stang, P. J.; Tetrahedron Lett. 1990, 31, 703. (10) In the interest of clarity, the schemes and eqs in thie paper show the iodine(II1) atom covalently bound to the triflate oxygen (I-OTD. However, such bonds are more ionic (I+OTf)than coyalent (see ref Sa, 6, and the X-ray structure of 21 in this work), and the triflates may be fully dissociated under some conditions.
OO22-3263/92/ 1957-6496$03.OO/O 0 1992 American Chemical Society
Propargylation of Iodine Complexes
J. Org. Chem., Vol. 57, No.24, 1992 6497
(which we assumed to possess an E configuratione)from the reaction of 3-hexyne with 2 (eq 3).
Scheme I1
7
Phi-
*iPh
T p n PhI--O-IPh
3
2
We then treated 3 with a variety of bases in an effort to deprotonate the carbon fl t- the iodonio leaving group and form an allenyl triflate. The result, however, was largely the regeneration of 3-hexyne (Scheme I). We then treated the propargylsilane 4a and the propargylstannane 4b with 2. We expected that the iodonium-bridged intermediate 6 would be most stable as the carbocation 6 stabilized by fl silicon or tin," and we thus expected the product of the reaction of 4 and 2 to be 7 as depicted in Scheme 11. (We hoped to desilylate or destannylate 7 to the allenyliodinane 8.) To our surprise the result, shown in eqs 4 and 5, was the formation of the rearranged propargyliodoarene 9.
+
ZMe.$iif
+
tl, 2
4
M
I2
+
It
L
8
Mc$iOSi
10
It
7
Scheme I11
H20 I
While we were investigating the mechanism of the formation of 9 and the reasons why 4a and 4b reacted differently with 2, Ochiai and co-workers published their observation that propqgliodoarenes were generated from the reaction of monoaryl i o d i i e s with propargylsilanes, -germanes, or -stannanes.12 They proposed that desilylation of an iodonium cation intermediate led to an allenyl iodinane and that an iodonio Claisen rearrangement of the latter led to 9 (Scheme III).12 Although they were unable to isolate the allenyliodinane, they did (i) find that the propargyliodoarenes were formed intramolecularly,12(ii) determine the regioaelectivity of the orthopropargylation of some ring-substituted monoaryl iodinanes,12and (iii) isolate mete-substituted propargyl iodoarenes (and in some cases ipso-substituted propargyl arenes) when both ortho positions of the monoaryl iodinane substrate were occupied by alkyl s~bstituents.'~J~ In this paper we explore the differences between the reaction of the propargylsilane 4a with 2 (eq 4)and that of the propargylstannane 4b (eq 5). We also report a deuterium labeling result that establishes the site of propargylation of 2 in the absence of substituents and the intramolecular kinetic isotope effect for the ortho~~
(11) For examples of the
4 effect of Si, Ge, end Sn: (a) Ullrich, H.;
Kaufmann, F. P.; Apeloig, Y.; Braude, V.; Danovich, D.; Bemdt, A.; Stamatis, N. Angew. Chem., Znt. Ed. Engl. 1991, 11,1479. (b) Nguyen, K.A.; Gordon, M. S.; Wang, G.; Lambert,J. B. Organometallics 1991, 10, 2798. (c) Dallaire, C.; Brook, M. A. Organometallics 1990,9, 2873. (12) Ochiai, M.; Ito, T.; Tekaoka, Y.; Masaki, Y. J . Am. Chem. SOC. 1991,113,1319. (13) Ochiai, M.; Ito, T.; Mesaki, Y. J. Chem. SOC.,Chem. Commun. 1992, 15.
4a
/W1
Q.,
-AcOH
9I +
948 h, degassed by freezing at -196 OC, evacuating, and thawing three times, and finally transferred into a flame-dried vacuum bulb. iodosylbenzene,32 4 , 4 D i m e t h y l - l - ( t r ) - 2 - p e n ~(4a),3' e were prepared by standard procedures. and Low-Temperature Reaction of 4a with Zefirov's Reagent (2). The propargylsilane 4a (55 rL, 0.277 mmol) was added by syringe to a 5mm NMR tube containing 2 (100 mg, 0.139 "01) and CDzClzby vacuum transfer (-0.7 mL) at -90 "C (EtOH/ liquid Nz slush bath). The solution was degassed, thawed at -90 OC, and sealed. The NMR tube containing the heterogeneous mixture was introduced into an NMR probe precooled to -90 OC and allowed to warm to -80 "C. The N M R revealed iodobenzene, hexamethyldisiloxane (12; 'H NMR: 6 0.01 (8). 13C NMR: 6 4-24), Me3SiOTf (10; 'H NMR 6 0.44 (e). 1%2 NMR: 6 1.25), 4,4-dimethyl-l-(2-iodophenyl)-2-pentyne'2 (9; 'H NMR: 6 7.77 (d), 7.66 (a),7.35 (m, overlaps with the proton in the para position of iodobenzene),6.95 (t),3.49 (s), 1.21 (a)), and tert-butylallene (11; 'H NMR-: 6 5.08 (dd, J = 6.6 Hz), 4.69 (d, J = 6.6 Hz), 0.97 ( 8 ) . 13CNMRmb: 6 204.8, 97.7, 72.1). The presence of 10 and 12 was confirmed by the addition of authentic samples to the product mixture at room temperature. 4,4-Dimethyl-l-(tributylstannyl)-2-pentyne (4b). In our hands, the reported method for the preparation of 4bu afforded substantial amounts of Bu,Sn as well as the desired product; a modified preparation of 4b follows. n-Butyllithium (6.9 mL, 17.3 mmol, 2.5 M) was added over 10 min to a solution of 4,4-diand THF (15 mL) while the methyl-2-pentyne (3 mL, 22.4 "01) temperature was maintained at -7 "C. After being stirred for 15 minutea, the solution was warmed to room temperatureand stirred for 1h. The resulting solution was cooled to -7 "C, treated with BuanCl(3.6 mL, 13.25 mmol), and warmed to room temperature. After 30 min, the solution was poured into 50 mL of saturated NH4Cl-50 mL of ether, and the aqueous phase w a ~extracted with ether (3 x 50 mL); the combined extracts were washed with brine and then dried over MgSO,. The solvents were removed and the reaidue spotted on a Chromatotron plate and eluted with pentane. Bu,Sn (R,0.47) and 4b (Rr 0.27) were separated. Compound 4b was Kugelrohr distilled (bp 87-93 "C (0.02 Torr)) to yield 3.32 g (65%). 'H NMR (CDC13): 6 1.50 (m, 6 H), 1.48 (s,2 H), 1.31 (m, 6 H), 1.16 (s,9 H), 0.90 (m, 15 H). 13CNMR (CDCld: 6 86.7, 78.4, 31.7, 29.0 (3Jcsn= 10.21 Hz), 27.7, 27.3 ('Jcs,, = 26.51 Hz), 13.6,9.8 ('JCsn= 253.52 Hz), -4.1. IR (neat): 2219 cm-' (-1. Anal. Calcd for C19H38Sn:C, 59.24; H, 9.94. Found C, 59.25; H, 9.94. Preparation of 4,4-Dimethyl-l-(2-iodophenyl)-2-pentyne (9)12from the Treatment of 2 with 4b. A suspension of 2 (804 mg,1.11"01) in CHC1, (10.0 mL) was prepared in a flamedried 25-mL Schlenk flask under NP The suspension was cooled to -30 OC (EtOH/liquid Nz slush bath) and treated with 4b (857 mg, 830 rL, 2.22 mmol). The GC yield of 9 was 558 mg (84%). 'H and 13C NMR spectra of the reaction mixture revealed the presence of 11 (4-8%).= The IR spectrum showed 1955 cm-l for (29) When fluoride ion WBS added to (E)-&alkylvinyliodonium tetrafluoroboratee, Ochiai and co-workers observed the selective attack on the alkylidene proton rather than the iodine(II1) center; see ref 3a. (30) Shriver, D.F. The Manipulation of Air Sensitiue Compounds; McGraw-Hilk New York, 1969. (31) Brand", L.;Verkruijese, H. Preparatiue Polar Organometallic Chemistry 1; Springer-Verlag: New York, 1987; p 64. (32) Saltzman, H.;Sharefkin, J. G. Organic Synthesis; Wiley: New York, 1973; Collect. Vol. V, p 658. (33) (a) Lilje, K.C.; Macomber, R. S. J. Org. Chem. 1974,24,3600. (b) Jawen, R.H. A. M.; Lousberg, R. J. J. Ch.; deBie, M. J. A. Recl. Trau. Chim. Pays-Bas 1981,100,85. (34) Rajagopalan, S.; Zweifel, G. Synthesis 1984, 111.
J. Org. Chem., Vol. 57, No.24, 1992 6601 the c--c--C asymmetric s t r e t ~ h The . ~ 'H and 'W N M R of the same mixture agreed with that of the authentic sample of Bu3SnOTf (16) described be10w.l~ The 'H NMR revealed 54% of 9 to 46% of 16. The CHC13was removed in vacuo and hexane (20mL) added to the residue. The upper layer was removed with a 2-mL glass pipette; the lower layer was extracted with hexane (3 X 15 mL), and the combined extracts were washed with brine and then dried over MgSO,. The hexane was removed, and the residue was Kugelrohr distilled (0.02 Torr, bp W 5 "C) to yield 357 mg (54%) of 9 with >95% purity (as determined by 'H NMR). The comparison of 'H N M R chemical shifts of iodobenzenfl with the chemical shifts and multiplicities in the phenyl region of 9 were used to assign the 'H NMR chemical shifta of the protons at positions 3-6 of 9; the doublets must correspond to H3 and H6, and the former can be distinguished by the fact that it collapses to a singlet when H4 is replaced by deuterium (see below). 'H NMR (CDCl,): 6 7.83 (H6, d, 1H), 7.64 (H3, d, 1H), 7.36 (H4, t, 1H), 6.94 (H5, t, 1H). "C NMR (CDCl3): 6 140.3, 139.1,128.9,128.3,128.1,99.8,92.7,75.4,31.5,31.3,27.6.IR (neat): v2204 cm-'. Tributylstannyl triflate (16) was prepared as described.16 'H NMR (CDC13): 6 1.63 (m, 6 H), 1.36 (m, 12 H), 0.90 (t, J = 7.27 HZ,9 H). '9C NMR (CDCld: 6 27.3 ('Jcs, = 13.22 HZ),26.7 ('Jcs,, 37.22 Hz), 21.3 ('Jcsn = 183.8 Hz), 13.3. 'gF NMR (CDC13): 6 -78.1. 2-p,p'-dz was prepared as described7c from p-deuterioiodosylbenzene. The latter was made by the procedurea standard for its isotopically normal analogue from pdeuterio(diacetoxy)iodobenzene, itself prepared by the procedurea standard for its isotopically normal analogue from p-deuterioiodobenzenel*('H NMR (CDC13): 6 7.45 (d, 2 H), 7.09 (d, 2 H). '9c N M R (CDC13): 6 137.5, 130.1, 127.1 (t, J = 25 Hz), 94.3. IR (neat): YC-D2252 cm-') and p-deuteriobromobenzene18('H NMR (CDC13): 6 7.39 (d, 2 H), 7.12 (d, 2 H). "C NMR (CDC13): 6 131.5,129.9,126.6 (t,J = 24 Hz),122.5. IR (neat): V ~ 2255 D cm-'. 'H N M R of the pdeuteriobromobenzeneshowed >99% deuterium incorporation). 9-4-dl. The procedure for this reaction was similar to that described above for the treatment of 2 with 4b with the exception that CHC13 was replaced with CHzClzand 2 was replaced with 2-p,p'-d,. The 'H NMR of the isolated 9-4-dl (recall that the GC yield of 9 in this reaction, determined above is 84%) revealed (>99%) a 1:l:lratio of a doublet (H6)-the proton ortho to the iodine in 9, a singlet (H3)-the proton ortho to the propargyl moiety of 9, and a doublet (H5)-the proton para to the propargyl moiety in 9; the assignments of the ring protons of 9 have been discussed above in connection with its preparation. 'H NMR (CDC13): 6 7.80 (H6, d, 1H), 7.61 ( H ~ , s1, H), 6.92 (H5, d, 1H), 3.58 (s,2 H), 1.28 (8, 9 H). 'V NMR (CDClJ: 6 140.4,139.2,128.9, 128.1,128.4 to 127.7 (apparent t overlapped with 6 128.1, J = 49 Hz), 99.8, 31.5, 31.3, 27.6. 2 - 0 , d - d ~was prepared from o-deuterioiodobenzene by the method described above for the generation of 2-p,p'-dz. The was prepared by required precursor o-de~teriochlorobenzene~~ quenching the o-lithiochlorobenzeneanion with a 2-fold excess of CH30D. The spedra of o-deuteriochlorobenzenenot previously reported were as follows. 'H NMR (CDCIJ: 6 7.40-7.24 (m). '9C N M R (CDClJ: 6 134.3,129.6,129.5,128.6,128.3,126.3(apparent t overlapped with 6 128.3, J = 25 HZ). Its 'H NMR showed >99% deuterium incorporation. o-Deuterioiodobenzene was prepared from o-deuteriochlorobenzeneby a reported procedurelgwith the following modifications. Magnesium metal (1.39 g, 56.2 mmol) in THF (25 mL) was treated with o-deuteriochlorobenzene (5.99 g, 52.7 "01) and was refluxed for 36 h. To the Grignard reagent was added a saturated Iz/anhydrous ether solution (70 mL, 66.2 "01) at -7 "C over a 45min period. The workup procedure was similar to that described for the isolation of p-deuterioiodobenzene.18 For o-deuterioiodobenzene. 'H NMR (CDC13): b 7.69 (d, 1H), 7.29 (t, 1H), 7.12-7.06 (m, 2 H). 13CNMR (CDC13): 6 137.4,137.0 (apparent t overlapped with S 137.4, J = 25 Hz),130.1, 129.9, 127.3, 94.2. (35) Silveratein, R. M.; Bawler, G. C.; Morrill, T. C. Spectroscopic Identification of Organic Compounds; Wiley: New York, 1981; p 231. (36) Sharefkin, J. G.; Saltzman, H. Organic Synthesis; Wiley: New York, 1973; Collect. Vol. V, p 660. (37) See ref 31, p 213.
J. Org. Chem. 1992,57,6502-6508
6502
IntramolecularKinetic Isotope E f f w . 2-0,0'-d2 + 4b. This reaction was carried out by the procedure described above for 9-4-dlwith the exception that 2-pg'-dz was replaced with 2-0,0'-4. The intensities of the m / e 298-300 peaks of the 9/9-6-d1 mixture were used to determine the value of 9/9-6-d1by an overdetermined least-squares procedure (program Massspec): (EI, 70eV) m/z (intensity) 298 (632), M, 299 (732), M + 1; 300 (91), M + 2. For 9/9-6-d1. 'H NMR (CDC13): S 7.79 (H6, d, 1 H), 7.62 (H3, d, 2 H), 7.35 (H4, t, 2 H), 6.92 (H5, m, 2 H), 3.58 (8, 4 H), 1.28 (a, 18 H). '% N M R (CDcld: S 140.1,139.1,138.4 (apparent overlapped with 6 139.1,J = 25 Hz),128.9,128.3,128.1,128.0,99.8,99.7,92.7, 75.3, 31.5, 31.3, 27.5. 2-Butynyl (Trimethylsily1)methyl Ether (20). To a wellin anhydrous stirred mixture of NaH powder (3.37 g, 140.4 "01) ether (50 mL) was added 2-butyn-1-01 (6.56 g, 93.6 mmol) over a 1-hperiod, the mixture was then allowed to stir for an additional 3 h. To this gray slurry was added Me3SiCH20W(18 mL, 90.0 "01) in anhydrous ether (50 mL) over a 45-min period and the stirring continued for an additional 24 h. The solution was cautiously added to a 1:l ether/CH30H solution until the exothermicity of the reaction ceased. The layers were separated, the aqueous phase was extracted with ether (3 X 75 mL), and the combined extracts were washed with brine and then dried over MgSO,. The ether was removed by evaporation and the residual oil distilled (bp 50 OC (10 Torr)); isolated yield, 11.7 g (80%). 'H NMR (CDCl3): S 4.02 (q, J = 1.9 Hz, 2 H),3.13 (t, J = 1.4 Hz, 2 H), 1.83 (t, J 1.8 Hz, 3 H), 0.02 ( ~ , H). 9 "C NMR (CDC13): S 81.5, 75.7, 63.5, 62.3, 3.1, -3.3. The 'H NMR revealed >95% purity. Preparation of the Vinyliodonium Triflate 21. A suspenin CHzC12(30 mL) was prepared sion of 2 (1117 mg,1.55 "01) in a flame-dried 100-mL Schlenk flask under NP To the lemon-yellow suspension was added 20 (266 mg, 1.70 mmol) whereupon the solution turned homogeneous lemon-yellow. After 48 h the mixture became cloudy as a white precipitate formed. The solvent was concentrated to 5 mL. A layer of anhydrous hexane (15 mL) was added. The resulting off-white precipitate was isolated by filtration (632 mg, 63%) and dried under vacuum (0.001 Torr) overnight. Crystals suitable for X-ray structure determination were grown out of a 101 ethyl acetate/hexane mixture; the crystah obtained (clear,colorlees needles) were dried overnight and then mounted on the diffracbmeter under a stream of NP 'H NMR (CD2Cl2): 6 8.15 (d, 2 H), 7.73 (t, 1 H), 7.54 (t, 2 H), 4.28 (a, 2 H), 3.29 (a, 2 HI, 2.66 (e, 3 H), 0.09 (a, 9 HI. 13C NMR (CD2C12): S 155.0,135.7,133.4,132.8,121.2,112.7,71.2,66.9, 23.2, -3.0. '@FNMR (CD2C12):6 -73.8, -78.7. Anal. Calcd for c, 29.19; H, 3.21; F, 17.31; I, 19.28; s, 9.74; si, C16H21F6107S2Si: 4.27. Found C, 29.01;H, 3.12; F, 17.28; I, 19.45; S, 9.70; Si, 4.10. X-ray Analysis of 21. C1 H21F6107S2Si, M = 658.4; monoclinic, C2/c, a = 29.431 (14) b = 8.364 (2) c = 22.328 (5) A, fl = 108.24 (2)O, V = 5220 (3) A3, 2 = 8, D, = 1.68 g ~ m - h~ ; (Mo Ka) = 0.7107 A, p = 1.51 mm-l, F(000)= 2608, T = 143 K,
1,
A,
~~
(38) The alternative reagent MeSSiCH21Bffords the undesired alkyl and silyl ethers; see: Chakraborty, T. K.;Reddy, G. V. J. Chem. Soc., Chem. Commun. 1989,251.
R = 0.056 (wR = 0.063) for 3562 unique, observed reflections. Crystal size 0.12 X 0.12 x 0.50 mm. Siemens P4 diffracbmeter, unit cell constants from least-squares fit of setting angles for 25 reflections (28, = 20.76'). Data collected (w scans) to (sin 8)/A = 0.5947 A-', -36 I h 5 0, -10 5 k I0, -27 I 1 I 27. Three standard reflections (200, 020, 002) every 97; Lorentz and polarization corrections;semiempiticalabsorption correction applied, maximum transmkaion = 0.720, minimumtransmission = 0.689;39 4584 unique reflections, 3562 reflections with F, > 2.5a(F0)observed. Structure solved by direct methods. Full-matrix (298 parameters total, data/parameters = 12.0) weighted [w = ($(I?) + gZV, g = 1.3 X 10-41leaetsquares refinement on F. H atoms in idealized positions (C-H = 0.96 A, U(H) = 1.2 X Uh(C)). Non-H atoms refined with anisotropic thermal parameters. At convergence ((A/a), = 0.012, (A/&, = 0.002 for last 3 cycles) R = 0.066, WR= 0.063,S = 1.11, & (,) = 1.4 e A4 (near I1 (0.75 A)), (&)& = -0.62 e A-3. Neutral atom scattering factors and anomalous dispersion correctionswere used,& all calculations were performed using the SHELXTL program library.* Attempts to Desilylate 21.% A suspension of 18-crown-6(240 mg,0.911 "01) and anhydrous KF (240 mg,4.13 "01) in CDC13 (3 mL) was prepared in a flame-dried 15mL Schlenk flask under N1. To the suspension was added 21 (204 mg, 0.310 mmol), and the white slurry was stirred for 18 h. The volatile components were vacuum transferred (0.001 Torr) into a h e - d r i e d 15mL 9N M R Schlenk flask. The only products identifiable by 'H and ' were iodobenzene and the propargyl ether 20. IR analysis of the nonvolatile and volatile components showed no evidence for an allene (no asymmetric C = C = C stretch in the 2000-1900 cm-l region). Similar results were obtained when KF.2Hz0 (94 mg, 1.00 "01) and Bu,NCl(ll39 mg,4.1 "01)~ in CD3CN (5 mL) were treated with 21 (724 mg,1.10 mmol). No evidence for an allene was seen in the IR when BQNF (TBAF) (720 pL, 0.720 mmol, 1.0 M) was stirred with a solution of 21 (233 mg, 0.354 mmol) in THF (2.5 mL) for a month.
Acknowledgment. We acknowledge Don Dick and David K.Morita for collecting the mass spectrum of 91 9 - 6 4 and helping with the GC analyses. We also thank Jonathan Filley, Christophe Lawrie, and David Collum (Cornell) for helpful discussions. This work was funded by Department of Energy Grant DE-FG02-84ER13299AOO8. Supplementary Material Available: Tables of X-ray crystal and structural data for 21 (9 pages). This material is contained in many libraries on microfiche, immediately follows this article in the microfilm version of the journal, and can be ordered from the ACS see any current masthead page for ordering information. (39) Sheldrick, G.M. SHELXTL,Unix Ver. 4.2; Siemens Analytical X-Ray Instruments, Inc.; Madison, WI, 1991. (40) International Tables for X-Ray Crystallography; Kynoch Birmingham,England, 1974; Vol. IV.
A Novel Synthesis of 2-Aminochromones via Phosgeniminium Salts Joel Morris,* Donn G. Wishka, and Yue Fang Medicinal Chemistry Research, The Upjohn Company, Kalamazoo, Michigan 49001
Received June 25, 1992
A novel method for the synthesis of antiplatelet 2-aminochromones making use of the reaction of 2'hydroxyacetophenone-BFz complexes with phosgeniminium chlorides has been developed. Aqueous hydrolysis of the intermediate j3-chlorovinylogous amide-BF2 complex affords the 2-aminochromone in good yield, without the need for chromatographic purification.
Interest in the 2-aminochromone class of compounds relates to ita novel antiplatelet activity.'T2 Research in this 0022-3263/92/1957-6502$03.00/0
area may lead to novel agents useful for the treatment of unstable angina or as adjuncts to conventional thrombo0 1992 American Chemical Society
